Hoeldtke R D, Bryner K D, Komanduri P, Christie I, Ganser G, Hobbs G R
Department of Medicine, West Virginia University, Morgantown 26506-9159, USA.
J Clin Endocrinol Metab. 2000 Feb;85(2):585-9. doi: 10.1210/jcem.85.2.6362.
It is well documented that diabetic patients with chronic complications have decreased renin secretion and elevations in the renin precursor prorenin. It is uncertain, however, whether the abnormal processing of prorenin is reflective of microvascular disease, hypertension, or autonomic neuropathy. Dechaux et al. (Transplant Proc. 18:1598-1599, 1986) observed abnormalities in prorenin processing in uncomplicated diabetes and suggested that it was the result of subclinical autonomic neuropathy. To test this hypothesis, we measured renin, prorenin, and autonomic function in early type 1 diabetes at a time when there is little or no microvascular disease or hypervolemia. Thirty-seven patients (10 males, 27 females) enrolled 2-22 months after diagnosis in a longitudinal study in which renin, prorenin, and autonomic function were measured annually for 3 years. Forty-one age-matched control subjects were also studied. PRA in the diabetic patients at the time of the second and third evaluations was 1.71 +/- 0.24 ng angiotensin I/mL x h and 1.67 +/- 0.24 ng angiotensin I/mL x h, respectively, significantly lower (P < 0.05) than that of the control subjects in whom PRA was 2.96 +/- 0.38 ng angiotensin I/mL x h. Prorenin was not different in the diabetic patients in comparison with controls. The renin to prorenin ratio in the diabetic patients at the time of the first, second, and third evaluations was 0.260 +/- 0.03, 0.235 +/- 0.05, and 0.227 0.05, respectively, significantly lower (P < 0.01) than in control subjects in whom the renin to prorenin ratio was 0.475 +/- 0.08. Despite this, at the time of the first and second evaluations, there was no evidence of autonomic dysfunction and no correlation between any test of autonomic function and the renin to prorenin ratio. At the time of the third evaluation, however, the intermediate frequency (0.04-0.15 Hz) power spectra while patients were supine (an index of sympathetic modulation of heart rate variability) showed a highly significant (P < .001) correlation with the renin to prorenin ratio. High frequency (0.15-0.40 Hz) spectra from supine patients at the third evaluation also correlated with the renin to prorenin ratio (P < 0.01). We conclude abnormal processing of prorenin develops in diabetic patients prior to microvascular disease, even before the first evidence of autonomic dysfunction. Although the latter may play a contributory role, additional as yet unidentified mechanisms seem to interrupt the processing of prorenin in early diabetes.
有充分的文献记载，患有慢性并发症的糖尿病患者肾素分泌减少，肾素前体（即血管紧张素原）水平升高。然而，血管紧张素原的异常加工是否反映微血管疾病、高血压或自主神经病变尚不确定。德肖等人（《移植过程》，18:1598 - 1599，1986年）观察到无并发症糖尿病患者血管紧张素原加工存在异常，并认为这是亚临床自主神经病变的结果。为验证这一假设，我们在1型糖尿病早期几乎没有或不存在微血管疾病或血容量过多时，测量了肾素、血管紧张素原和自主神经功能。37例患者（10例男性，27例女性）在诊断后2 - 22个月纳入一项纵向研究，在3年中每年测量肾素、血管紧张素原和自主神经功能。还研究了41例年龄匹配的对照受试者。糖尿病患者在第二次和第三次评估时的血浆肾素活性（PRA）分别为1.7 I±0.24 ng血管紧张素I/mL·h和1.67±0.24 ng血管紧张素I/mL·h，显著低于（P < 0.05）对照受试者，对照受试者的PRA为2.96±0.38 ng血管紧张素I/mL·h。糖尿病患者的血管紧张素原与对照相比无差异。糖尿病患者在第一次、第二次和第三次评估时的肾素与血管紧张素原比值分别为0.260±0.03、0.235±0.05和0.227±0.05，显著低于（P < 0.01）对照受试者，对照受试者的肾素与血管紧张素原比值为0.475±0.08。尽管如此，在第一次和第二次评估时，没有自主神经功能障碍的证据，自主神经功能的任何检测与肾素与血管紧张素原比值之间也没有相关性。然而，在第三次评估时，患者仰卧位时的中频（0.04 - 0.15 Hz）功率谱（心率变异性交感神经调节指标）与肾素与血管紧张素原比值呈高度显著（P < 0.001）相关。第三次评估时仰卧位患者的高频（0.15 - 0.40 Hz）谱也与肾素与血管紧张素原比值相关（P < 0.01）。我们得出结论，在微血管疾病之前，甚至在自主神经功能障碍的首个证据出现之前，糖尿病患者就已出现血管紧张素原加工异常。虽然后者可能起一定作用，但似乎还有其他尚未明确的机制在早期糖尿病中干扰了血管紧张素原的加工。
